Rituxan Effective in Refractory RA

Action Points

Patients with rheumatoid arthritis who fail on treatment with a tumor necrosis factor (TNF) inhibitor may have a better response if they switch to rituximab (Rituxan) rather than trying a second TNF blocker, a study has found.

Note that rituximab differs from the TNF inhibitors, which target an inflammatory cytokine, in that its mechanism of action is through depletion of B cells.

Patients with rheumatoid arthritis who fail on treatment with a tumor necrosis factor (TNF) inhibitor may have a better response if they switch to rituximab (Rituxan) rather than trying a second TNF blocker, a comparative analysis suggested.

Patients who began taking rituximab were significantly more likely to have a moderate or good response on the clinical criteria established by the European League Against Rheumatism (EULAR), with an odds ratio of 1.31 (95% CI 1.02 to 1.69, P=0.04), according to Darren M. Ashcroft, PhD, and colleagues from the University of Manchester in England.

Those who switched also had a greater chance of having a significant improvement in physical function (OR 1.49, 95% CI 1.07 to 2.08, P=0.02), the researchers reported in the August Arthritis Care & Research.

As therapeutic options for rheumatoid arthritis have proliferated, the clinical dilemma of choosing among them has arisen.

About one-third of patients stop anti-TNF therapy within a year, either because of adverse effects or a lack of efficacy.

Some of these patients have done well on another TNF inhibitor, but one earlier study suggested that disease activity and inflammation might be more favorable if patients switched to rituximab.

Rituximab differs from the TNF inhibitors, which target an inflammatory cytokine, in that its mechanism of action is through depletion of B cells.

To compare the two strategies, Ashcroft's group analyzed data from the British Society for Rheumatology Biologics Register for patients who had adequate data on either the Disease Activity Score in 28 joints (DAS28) or the Health Assessment Questionnaire (HAQ).

The two types of patient data were analyzed separately to increase the statistical power.

Because this was not a randomized study, the researchers calculated propensity scores to account for differences at baseline between patients who used a second TNF inhibitor and those who switched to rituximab.

The primary outcome was EULAR response, which relies on the change in DAS28 and the level of DAS28 achieved to determine if patients are good, moderate, or nonresponders.

Among patients analyzed according to DAS28 data -- reflecting disease activity -- 941 had switched to a second TNF inhibitor and 387 began treatment with rituximab.

The rituximab group tended to be older, had higher DAS28 scores (6.2 versus 5.9, P<0.001), and were more likely to have comorbidities.

Among patients with HAQ data -- reflecting patient-reported physical function -- 693 used a second TNF inhibitor and 244 switched to rituximab.

For these patients, those on rituximab again were older and had more comorbidities.

In the disease activity analysis, changes in DAS28 scores were similar, at −1.3 in patients on rituximab and −1.2 in those on an alternate TNF inhibitor.

However, EULAR response rates were higher in the rituximab group, with 17.1% having good responses, 37.7% having moderate responses, and 45.2% being nonresponders.

Corresponding rates in the alternate TNF group were 13.5%, 33.8%, and 52.7%, the researchers reported.

Actual remission was more common in the anti-TNF group, though not significantly so (10.4% versus 7.2%, P=0.07).

This may have been related to baseline differences in DAS28 scores, according to the researchers, and once baseline characteristics were adjusted for in the propensity score calculation, there was a significantly greater likelihood for a moderate or good response with rituximab.

In the analysis according to physical function, the changes in HAQ score were similar, at −0.11 in patients on a second TNF inhibitor and −0.13 in the rituximab group.

But patients in the rituximab group more commonly achieved a 22-point minimum clinically important improvement in their HAQ scores (38.4% versus 29.6%, P=0.01).

However, the majority of patients on both treatments did not have a clinically important improvement in physical functioning, "which may suggest an irreversible physical disability in those patients who already have failed 1 anti-TNF therapy," Ashcroft and colleagues observed.

Limitations of this analysis included a lack of information as to whether treatment failure was considered primary or secondary, and inadequate data to explore factors that might predict response.

In addition, it included only patients who had failed a single TNF inhibitor, and in clinical practice patients may have taken two or more of these agents.

Future research will be needed to assess responses in patients with multiple previous TNF inhibitors, and also to examine the effects of switching to newer agents such as abatacept (Orencia) and tocilizumab (Actemra).

"These results suggest that, in clinical practice, for patients who had failed a first anti-TNF therapy, it may be better to start [rituximab] at this point rather than switching to a second anti-TNF therapy," the researchers concluded.

The British Society for Rheumatology receives support from Abbott, Amgen, Roche, Schering-Plough, and Wyeth.

Soliman is supported by the government of Egypt.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner